PMID- 34801078
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211125
IS  - 1758-5996 (Print)
IS  - 1758-5996 (Electronic)
IS  - 1758-5996 (Linking)
VI  - 13
IP  - 1
DP  - 2021 Nov 20
TI  - Leucine imparts cardioprotective effects by enhancing mTOR activity and 
      mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model.
PG  - 139
LID - 10.1186/s13098-021-00755-z [doi]
LID - 139
AB  - BACKGROUND: Coronary artery disease is a leading cause of morbidity and mortality 
      among patients with diabetes. Previously, we demonstrated that branched-chain 
      amino acids (BCAAs) showed cardioprotective effects against cardiac 
      ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a 
      BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) 
      activity and mitochondrial function. However, whether Leu has cardioprotective 
      effects on diabetic hearts is unclear. In this study, we examined the 
      preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese 
      mouse which simulate prediabetic heart. METHODS: In vivo mice models of I/R 
      injury were divided into the following groups: control, mTOR(+/-), and high-fat 
      diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the 
      mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were 
      subjected to simulated I/R injury. Biochemical and mitochondrial functional 
      assays were performed to evaluate the changes in mTOR activity and mitochondrial 
      dynamics caused by Leu treatment. RESULTS: Leu-treated mice showed a significant 
      reduction in infarct size when compared with the control group (34.8% +/- 3.8% vs. 
      43.1% +/- 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the 
      protective effects of Leu. This preconditioning effect of Leu was attenuated in 
      mTOR(+/-) mice. Additionally, Leu increased the percentage of fused mitochondria 
      and the mitochondrial volume, and decreased the number of mitochondria per cell 
      in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment 
      significantly reduced infarct size (41.0% +/- 1.1% vs. 51.0% +/- 1.4%, n = 7, 
      p < 0.05), which was not induced by ischemic preconditioning, and this effect was 
      inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and 
      mitochondrial fusion with decreased reactive oxygen species production with Leu 
      treatment in HFD-induced obese mice, but not in mTOR(+/-) mice. CONCLUSIONS: Leu 
      treatment improved the damage caused by myocardial I/R injury by promoting mTOR 
      activity and mitochondrial fusion on prediabetic hearts in mice.
CI  - (c) 2021. The Author(s).
FAU - Morio, Atsushi
AU  - Morio A
AD  - Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 
      Kasumi, Minami, Hiroshima, 734-8551, Japan.
FAU - Tsutsumi, Rie
AU  - Tsutsumi R
AD  - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, 
      Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
FAU - Satomi, Shiho
AU  - Satomi S
AD  - Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 
      Kasumi, Minami, Hiroshima, 734-8551, Japan.
FAU - Kondo, Takashi
AU  - Kondo T
AD  - Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 
      Kasumi, Minami, Hiroshima, 734-8551, Japan.
FAU - Miyoshi, Hirotsugu
AU  - Miyoshi H
AD  - Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 
      Kasumi, Minami, Hiroshima, 734-8551, Japan.
FAU - Kato, Takahiro
AU  - Kato T
AD  - Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 
      Kasumi, Minami, Hiroshima, 734-8551, Japan.
FAU - Kuroda, Masashi
AU  - Kuroda M
AD  - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, 
      Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
FAU - Kitamura, Tadahiro
AU  - Kitamura T
AD  - Laboratory of Metabolic Signal, Institute for Molecular and Cellular Regulation, 
      Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512, Japan.
FAU - Hara, Kenta
AU  - Hara K
AD  - Kita Harima Medical Center, 926-250 Ichiba, Ono, Hyogo, 675-1392, Japan.
FAU - Saeki, Noboru
AU  - Saeki N
AD  - Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 
      Kasumi, Minami, Hiroshima, 734-8551, Japan.
FAU - Sakaue, Hiroshi
AU  - Sakaue H
AD  - Department of Nutrition and Metabolism, Institute of Biomedical Sciences, 
      Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan.
FAU - Tsutsumi, Yasuo M
AU  - Tsutsumi YM
AD  - Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 
      Kasumi, Minami, Hiroshima, 734-8551, Japan. yasuo223@hiroshima-u.ac.jp.
LA  - eng
GR  - 19K09353/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20211120
PL  - England
TA  - Diabetol Metab Syndr
JT  - Diabetology & metabolic syndrome
JID - 101488958
PMC - PMC8606064
OTO - NOTNLM
OT  - Cardioprotective
OT  - High-fat diet
OT  - Leucine
OT  - Myocardial ischemia/reperfusion injury
COIS- The authors declare that they have no competing interests.
EDAT- 2021/11/22 06:00
MHDA- 2021/11/22 06:01
PMCR- 2021/11/20
CRDT- 2021/11/21 20:25
PHST- 2021/04/28 00:00 [received]
PHST- 2021/11/04 00:00 [accepted]
PHST- 2021/11/21 20:25 [entrez]
PHST- 2021/11/22 06:00 [pubmed]
PHST- 2021/11/22 06:01 [medline]
PHST- 2021/11/20 00:00 [pmc-release]
AID - 10.1186/s13098-021-00755-z [pii]
AID - 755 [pii]
AID - 10.1186/s13098-021-00755-z [doi]
PST - epublish
SO  - Diabetol Metab Syndr. 2021 Nov 20;13(1):139. doi: 10.1186/s13098-021-00755-z.